Well, it’s been a tough month for herbs since my last monthly soiree here at SBM.

Just last week at the American Society for Clinical Oncology (ASCO) meeting, a group out of the Mayo Clinic presented data from a study showing that a well-characterized flaxseed extract was ineffective against hot flashes in postmenopausal women. But as Steve Novella noted here earlier this week, negative clinical trials data on supplements rarely influence the behavior of those who continue to advocate for their herbal use.

Flaxseed, known to contain phytoestrogen compounds such as secoisolariciresinol diglucoside (SDG) and enterolactone, has been purported to relieve hot flashes.

But I think the hypothesis was flawed in the first place: while these compounds bind the estrogen receptor, they have largely been shown to be estrogen receptor modulators that act in a negative manner. Work from the group of Dr. Lillian Thompson at the University of Toronto has repeatedly shown in an estrogen-dependent animal model of human breast cancer that flaxseed components act in a predominantly anti-estrogenic manner. One might suspect that hot flashes would be made worse by flaxseed, although this was not the case in the study presented as ASCO.

However, flaxseed is definitely a great source of fiber and may have preventive effects in prostate cancer, but not through an estrogenic mechanism. Instead, another flaxseed component, the omega-3 fatty acid alpha-linoleic acid (ALA), reduces the conversion of testosterone to its more active form, dihydrotestosterone. This work comes from a former colleague at Duke University, Wendy Demark-Wahnefried, now at the University of Texas-M.D. Anderson Cancer Center.

Bottom line: A good understanding of the basic science of herbal medicines is absolutely essential to good clinical trial design.

Don’t Bogart My Brownies

A story that’s more likely to have been seen by SBM readers is Lazy Cakes, a dietary supplement-laden brownie intended as a sleep-aid (here’s an example from NPR). The implied undercurrent of this product, of course, is the longstanding tradition of baking marijuana into brownies to – uh – get baked. The packaging itself evokes memories of the Grateful Dead, Phish, and Widespread Panic – musical groups closely associated with marijuana use who the reader will identify with depending on their age. Their tagline, “Relaxation Baked In,” isn’t even a veiled association with this traditional herbal practice.

Lazy Cakes have created an uproar in part because they contain a dietary supplement with potential of central nervous system activity, melatonin. This naturally-occurring hormone is synthesized in the pineal gland and appears to regulate our circadian rhythms. The reader may best recognize melatonin for prevention of jet lag. It is, in simple terms, a sedative and appears to be more potent in younger people. National poison control centers report several thousand calls regarding melatonin each year, with the majority of reports of sedation in children who’ve gotten hold of a parents supplement. Here’s one example from the Texas Department of State Health Services.

Lazy Cakes might also be riding on the well-known Philadelphia-area delicacy, Tastykake. The fact that I have included Tastykake in a post about Lazy Cakes is most certainly not pleasing to this East Coast institution but I have yet to find anything in the Philadelphia press about this issue. (By the way, these wonders of the food world fueled my childhood development as well as my scientific training at the school known previously as the Philadelphia College of Pharmacy and Science.)

The concern with Lazy Cakes seems to be that each brownie contains 7.8 mg of melatonin, well above the generally recommended sleeptime dose of 1 to 3 mg. While there have been no controlled trials of Lazy Cakes, anecdotal reports suggest that the brownies do indeed have physiological action. From the NPR story:

“There is an effect with Lazy Cakes, but I wouldn’t say it’s comparable to marijuana at all,” says Niki D’Andrea, who bought one while at a shop that sells drug paraphernalia.

D’Andrea’s not shy about having tried both; it’s part of her job writing about subculture for the Phoenix New Times. She didn’t get high from the Lazy Cake, but she was shocked at how sleepy it made her.

“I really did go to bed for about, I think 10 to 12 hours after I ate that first Lazy Cake, so well, maybe I should have started with half,” D’Andrea says.

Actually, half is the recommended serving size. As if anyone ever just eats half a brownie.

Less attention has been given to the other herbal components: valerian and passionflower extracts.

Valerian (Valeriana officinalis L.) has been investigated for sleep-inducing and anti-anxiety effects. In fact, some of the same researchers who presented the ASCO work above on flaxseed conducted a Phase III trial of valerian extract in cancer patients. Published earlier this year in the Journal of Supportive Oncology, the study revealed that this valerian root extract had no effect on overall measures of sleep efficacy, although some beneficial effects were observed on secondary measures such as fatigue.

However, we have no idea what valerian might do together with this rather high dose of melatonin. Come to think of it, I have no idea how the manufacturer made a valerian-containing brownie even remotely palatable. I have a 16-year-old bottle of valerian root that I use for classroom demonstrations and it still smells of rancid gym socks. But, then again, baking valerian extract is likely to release some of these volatiles.

Less is known about passionflower (Passiflora incarnata). Even a Cochrane review of passionflower for anxiety was unable to come to a solid conclusion due to the low number of studies.

Another issue not addressed in most MSM reports is that the actual content of components can vary wildly from amounts listed on dietary supplement labels. In most cases, the products contain less but this inconsistency is concerning with a product that contains a human hormone well-known to induce sleep.

The bottom line: don’t mess with Lazy Cakes. As with any sedative drug – whether a supplement, prescription or over-the-counter – there’s always a concern for additive or synergistic effects with alcohol.

But rest assured that the uproar over Lazy Cakes will further fuel sales. And given dietary supplement regulations in the United States, I really don’t see this product being banned – although the manufacturer has added additional warnings about sedation and intended use by adults.

That’s right – a product featuring a sleepy brownie that resembles Spongebob Squarepants is intended solely for adults.

Posted by David J Kroll